Non-syndromic cleft lip and palate are common complex traits resulting from genetic and environmental risk factors. The genetic model that best explains non-syndromic clefting (NSC) is a multiplicative model under which a few genes with moderate effect operate against a multifunctional background to produce the clefting. Most genetic studies on NSC treat the clefting phenotype as a dichotomous trait, in that an individual is either affected of unaffected. Recent evidence suggests that family members of NSC patients are more likely to have various craniofacial dysmorphology. In this proposal, the principal investigator will define the craniofacial abnormalities in NSC patients and families by imaging and measurement of their craniofacial skeleton, and evaluate the mode of inheritance of specific dysmorphologic features in NSC families using complex segregation analysis. The principal investigator will also determine if the transmission of specific genetic alleles is associated with the transmission of specific craniofacial dysmorphologic features in NSC families using the transmission disequilibrium test. This is a novel approach to the mapping of a complex structural trait, in that a traditionally dichotomous trait (NSC) is broken down into a number of quantitative threshold traits (dysmorphologic features), each of which will then be analyzed individually. The genetic information will help future identification of environmental factors that contribute to these common birth defects. This proposal requests funds to support the research component of a fellowship proposal (F33 DE5757-01) submitted by this principal investigator.